Receptors for purine nucleotides, known as P2 purinergic receptors, mediate a number of potent and possibly important biological effects in the cardiovascular system. The P2X ion channels are receptor channels activated by extracellular ATP, while the P2Y receptors are G protein-coupled receptors. Together, they represent two sub-families of the P2 nucleotide receptors. Previous studies have shown that extracellular ATP can cause an ionic current in murine, rat and guinea pig cardiac ventricular myocytes. The receptor that mediates this current appears to be a P2X receptor, of which the P2X4 receptor is an important subunit. Activation of P2X receptors leads to the opening of a nonselective cation channel permeable to Na+, K+ and Ca2+. The current is inward at negative membrane potentials, reverses near 0 mV, and becomes outward at positive potentials. The continuous activation of this receptor channel by endogenous extracellular ATP may assume an important biological function. This constant activation under the resting or negative membrane potentials would produce an inward current, while its activation during depolarized portions of the action potential should lead to an outward current. These currents represent a possible ionic mechanism by which the cardiac P2X channel achieves its biological effects.
While activation of P2X receptors is known to mediate ion currents, little is known about the biological role of this ion current mediation. In addition, the effect of P2X receptor agonists on biological functions of P2X including cardiac function and contractility is not understood. There remains a need for the elucidation of the role of P2X receptors and their agonists on cardiac function and contractility.